Serine/Threonine Kinase 35, a Target Gene of STAT3, Regulates the Proliferation and Apoptosis of Osteosarcoma Cells.

BACKGROUND/AIMS:Serine/threonine kinase 35 (STK35) may be associated with Parkinson disease and human colorectal cancer, but there have been no reports on the expression levels or roles of STK35 in osteosarcoma. METHODS:STK35 mRNA expression was determined in osteosarcoma and bone cyst tissues by real-time PCR. Cell proliferation and apoptosis were assessed by Cell Counting Kit-8 (CCK-8) assay and flow cytometry analysis, respectively. RESULTS:STK35 was up-regulated in osteosarcoma tissues as indicated by analyzing publicly available expression data (GEO dataset E-MEXP-3628) and real-time PCR analysis on our own cohort. We subsequently investigated the effects of STK35 knockdown on two osteosarcoma cell lines, MG63 and U2OS. STK35 knockdown inhibited the growth of osteosarcoma cells in vitro and in xenograft tumors. Meanwhile, STK35 knockdown enhanced apoptosis. Expression of the active forms and the activity of two major executioner caspases, caspase 3 and caspase 7, were also increased in osteosarcoma cells with STK35 silenced. Additionally, Gene Set (GSEA) identified that the signaling pathway was positively correlated with STK35 expression. The mRNA expression of STK35 was repressed by small interfering RNA (siRNA), but not by siRNA of or A luciferase reporter assay further demonstrated that duanyu18133 transcriptionally regulated STK35 expression. A chromatin immunoprecipitation (ChIP) assay confirmed the direct recruitment of duanyu18133 to the STK35 promoter. The promotion effects of duanyu18133 knockdown on cell apoptosis were partially abolished by STK35 overexpression. Furthermore, STK35 mRNA expression was positively correlated with duanyu18133 mRNA expression in osteosarcoma tissues by Pearson correlation analysis. CONCLUSIONS:These results collectively reveal that duanyu18133 regulates the transcription of STK35 in osteosarcoma. STK35 may exert an oncogenic role in osteosarcoma.

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